Syntheses of Triostin A Antibiotic and Nucleobase-Functionalized Analogs as New DNA Binders

2009 ◽  
Vol 2009 (28) ◽  
pp. 4801-4809 ◽  
Author(s):  
Anmol Kumar Ray ◽  
Ulf Diederichsen
Keyword(s):  
Triostin A ◽  
Dna Binders

Advances in Spirocyclic Hybrids: Chemistry and Medicinal Actions

2018 ◽  
Vol 25 (31) ◽  
pp. 3748-3767 ◽  
Author(s):  
Mohammed Benabdallah ◽  
Oualid Talhi ◽  
Fatiha Nouali ◽  
Nouredine Choukchou-Braham ◽  
Khaldoun Bachari ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Apoptotic Cell ◽  
Structural Diversity ◽  
Antibacterial Activities ◽  
Innovative Drug ◽  
Neuroprotective Effects ◽  
Cellular Division ◽  
Bioactive Natural Products ◽  
Anaplastic Lymphoma ◽  
Dna Binders

The present review deals with the progress in medicinal chemistry of spirocyclic compounds, a wider class of natural and synthetic organic molecules, defined as a hybrid of two molecular entities covalently linked via a unique tetrahedral carbon. This spiro central carbon confers to the molecules a tridimensional structurally oriented framework, which is found in many medicinally relevant compounds, a well-known example is the antihypertensive spironolactone. Various bioactive natural products possess the privileged spiro linkage and different chemo-types thereof become synthetically accessible since the 20th century. Actually, there has been a growing interest in the synthesis of heterocyclic hybrids gathered via a spiro carbon. Most of these combinations are two moieties in one scaffold being able to interfere with biological systems through sequential mechanisms. Spirocyclic hybrids containing indole or oxindole units are compounds exhibiting higher interaction with biological receptors by protein inhibition or enzymatic pathways and their recognition as promising anticancer agents in targeted chemotherapy is foreseen. These specific, low-weight and noncomplex spirocyclic hybrids are potent inhibitors of SIRT1, Mdm2–p53 and PLK4, showing affinity for anaplastic lymphoma kinase (ALK) receptor. They are also known as excellent DNA binders, acting on cellular division by arresting the cell cycle at different phases and inducing apoptotic cell death. A structural diversity of spirocyclic hybrids has proved neuroprotective effects, anti-HIV, antiviral and antibacterial activities. Hundred of papers are mentioned in this review underlying chemical issues and pharmacological potencies of spiro compounds, which render them impressive synthetic hits for innovative drug conception.

DNA Binders: 1. Evaluation of DNA-Interactive Ability, Design, and Synthesis of Novel Intercalating Agents

2009 ◽  
Vol 6 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Mario Sechi ◽  
Marco Derudas ◽  
Roberto Dallocchio ◽  
Alessandro Dessì ◽  
Alessia Cosseddu ◽  
...  
Keyword(s):  
Design And Synthesis ◽  
Dna Binders ◽  
Intercalating Agents

Recent Progress in Polynuclear Ruthenium Complex-Based DNA Binders/Structural Probes and Anticancer Agents

2020 ◽  
Vol 27 (22) ◽  
pp. 3735-3752 ◽  
Author(s):  
Si-Qi Zhang ◽  
Li-Hua Gao ◽  
Hua Zhao ◽  
Ke-Zhi Wang
Keyword(s):  
Anticancer Agents ◽  
Ruthenium Complex ◽  
Ruthenium Complexes ◽  
Anticancer Activities ◽  
Bridging Ligands ◽  
Metal Centers ◽  
Dna Binders ◽  
Structural Probes ◽  
Polynuclear Ruthenium Complexes

Ruthenium complexes have stood out by several mononuclear complexes which have entered into clinical trials, such as imidazolium [trans-RuCl4(1H-imidazole)(DMSO-S)] (NAMI-A) and ([Ru(II)(4,4'-dimethyl-2,2'-bipyridine)2-(2(2'-,2'':5'',2'''-terthiophene)-imidazo[4,5-f] [1,10]phenanthroline)] 2+) (TLD-1433), opening a new avenue for developing promising ruthenium-based anticancer drugs alternative to Cisplatin. Polynuclear ruthenium complexes were reported to exhibit synergistic and/or complementary effects: the enhanced DNA structural recognition and DNA binding as well as in vitro anticancer activities. This review overviews some representative polynuclear ruthenium complexes acting as DNA structural probes, DNA binders and in vitro anticancer agents, which were developed during last decades. These complexes are reviewed according to two main categories of homo-polynuclear and hetero-polynuclear complexes, each of which is further clarified into the metal centers linked by rigid and flexible bridging ligands. The perspective, challenges and future efforts for investigations into these exciting complexes are pointed out or suggested.

scholarly journals Bifunctional intercalation and sequence specificity in the binding of quinomycin and triostin antibiotics to deoxyribonucleic acid

1978 ◽  
Vol 173 (1) ◽  
pp. 115-128 ◽  
Author(s):  
J S Lee ◽  
M J Waring
Keyword(s):  
Binding Constant ◽  
Binding Constants ◽  
Sequence Specificity ◽  
Peptide Antibiotics ◽  
Naturally Occurring ◽  
Binding Isotherms ◽  
Triostin A ◽  
Specificity Pattern ◽  
Intercalating Agents ◽  
Binding Curves

Quinomycin C, triostin A and triostin C are peptide antibiotics of the quinoxaline family, of which echinomycin (quinomycin A) is also a member. They all remove and reverse the supercoiling of closed circular duplex DNA from bacteriophage PM2 in the fashion characteristic of intercalating drugs, and the unwinding angle at I 0.01 is, in all cases, almost twice that of ethidium. Thus, as with echinomycin, they can be characterized as bifunctional intercalating agents. For the triostins this conclusion has been confirmed by measurements of changes in the viscosity of sonicated rod-like DNA fragments; the helix extension was found to be almost double that expected for a simple monofunctional intercalation process. For triostin A, further evidence for bifunctionality was derived from the cross-over point of binding isotherms to nicked circular and closed circular bacteriophage-PM2DNA. Binding curves for the interaction of quinomycin C and triostin A with a variety of synthetic and naturally occurring nucleic acids were determined by solvent-partition analysis, but triostin C was too insoluble in aqueous solution to make this method applicable. For quinomycin C the highest binding constant was found with Micrococcus lysodeikticus DNA, and its pattern of specificity among natural DNA species was broadly similar to that of echinomycin, although the binding constants were 2–6 times as large. For triostin A the highest binding constant was again found for M. lysodeikticus DNA, but the specificity pattern was quite different from that of the quinomycins. In particular, triostin A bound better to poly(dA-dT) than to the poly(dG-dC) whereas this order was reversed for quinomycin C. There was also evidence that the binding to poly(dA-dT) might be co-operative in nature. No significant interaction could be detected with poly(dA).poly(dT) or with RNA from Escherichia coli. Poly(dG).poly(dC) gave variable results, depending on the source of the polymer. The different patterns of specificity displayed by the quinomycins and triostins are tentatively ascribed to differences in their conformations in solution.

Origin of slow conformer conversion of triostin A and interaction ability with nucleic acid bases

2009 ◽  
Vol 21 (5) ◽  
pp. 541-545 ◽  
Author(s):  
NAOKI HIGUCHI ◽  
YOSHIMASA KYOGOKU ◽  
MASARU SHIN ◽  
KEN INOUYE
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Bases ◽  
Triostin A

Anticancer Activity of Novel Platinum Complex as DNA Binders

2013 ◽  
Vol 781-784 ◽  
pp. 1107-1110
Author(s):  
Xu Jian Luo ◽  
Qi Pin Qin ◽  
Yu Lan Li ◽  
Yan Cheng Liu
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Normal Cell ◽  
Platinum Complex ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Element Analysis ◽  
Normal Cells ◽  
Dna Binders ◽  
Ct Dna

A new phenanthroimidazole platinum (II) complex has been synthesized and characterized by IR, NMR, ESI-MS, element analysis. The affinities of the complex toward ct-DNA was determined by circular dichroism absorption (CD), UV-Vis absorption. Results indicate that the complex interact with ct-DNA by classical intercalating mode. The cytotoxicities of the complex was screened against four cancer cell lines and normal cells of HL-7702 in comparison to cisplatin and it showed a higher activity than cisplatin, with IC50 values in the range 8.7417.11 μmol/L. Furthermore, the complex displayed lower cytotoxic activities to HL-7702 (normal cell) compared with the cancer cell lines.

DNA–EB in agarose gel assay: a simple methodology in the search for DNA-binders in crude extracts from actinomycetes

2016 ◽  
Vol 8 (12) ◽  
pp. 2653-2659
Author(s):  
Anelize Bauermeister ◽  
Munira Muhammad Abdel Baqui ◽  
Luiz Alberto Beraldo Moraes
Keyword(s):  
Agarose Gel ◽  
Screening Process ◽  
Replication Studies ◽  
Crude Extracts ◽  
Dna Binders

Here, a methodology was proposed to detect DNA-binders in a screening process with crude extracts produced by actinomycetes, positive extracts were subjected to replication studies by LC-MS/MS.

Biologically active halo-substituted ferrocenyl thioureas: synthesis, spectroscopic characterization, and DFT calculations

2018 ◽  
Vol 42 (9) ◽  
pp. 7154-7165 ◽  
Author(s):  
Faiza Asghar ◽  
Sadaf Rana ◽  
Saira Fatima ◽  
Amin Badshah ◽  
Bhajan Lal ◽  
...  
Keyword(s):  
Dna Binding ◽  
Dft Calculations ◽  
Binding Affinity ◽  
Spectroscopic Characterization ◽  
Biologically Active ◽  
Dna Binding Affinity ◽  
Dna Binders

The DNA binding affinity of ferrocenyl complexes explored by CV and UV ascertain them as noble DNA binders. The computational measurements correlate well with the outcomes of electrochemistry and bio-activities.

scholarly journals Synthetic Studies on Quinoxaline Antibiotics. II. Synthesis of Triostin A

1984 ◽  
Vol 57 (8) ◽  
pp. 2203-2210 ◽  
Author(s):  
Masaru Shin ◽  
Ken Inouye ◽  
Hideo Otsuka
Keyword(s):  
Triostin A ◽  
Synthetic Studies
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